Phosphaturic Mesenchymal Tumor: 2 New Oral Cases and Review of 53 Cases in the Head and Neck

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm that secretes fibroblast growth factor-23 (FGF-23) and causes oncogenic osteomalacia. It occurs in adults with equal gender distribution and the most common location is the lower extremities, followed by the head and neck. Besides osteomalacia, the clinical presentation includes bone pain and multiple bone fractures. Microscopic features consist of spindle cells, multinucleated giant cells, and calcifications embedded in a chondromyxoid matrix. Laboratory findings indicate normal calcium and parathyroid levels, hypophosphatemia, and increased levels of FGF-23 that usually revert to normal after surgical removal. Due to its rarity, the purpose of the study was to report 2 new oral cases of PMT and to review the literature in the head and neck. The first case occurred in the gingiva and had been present for 6 years. The second case was a recurrence of a previously diagnosed PMT in the right mandible that metastasized to the lung and soft tissue. The literature review included 53 cases in the head and neck. There was a predilection for extra-oral sites (76 %) compared to intra-oral sites (24 %) with paranasal sinuses considered the most common location (38 %) followed by the mandible (15 %). There were 9 recurrences that included 3 malignant cases indicating a potentially aggressive tumor. Due to the indeterminate biological behavior of PMT and its rarity, a comprehensive evaluation of medical, laboratory, radiographic, and histological findings are crucial for a definitive diagnosis and treatment.     

Alteration of serum thymus and activation‐regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti‐interleukin‐17A agents

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side‐effects of biologics, dose‐reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation‐regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI‐clear with biologics than in the group which did not achieve PASI‐clear. Among biologics, the group treated with secukinumab, an anti‐interleukin (IL)‐17A agent, showed significantly higher TARC level compared with the group treated with anti‐tumor necrosis factor agents. In certain populations achieving PASI‐clear, serum TARC level may be a potent marker reflecting better response to IL‐17A inhibitors, and in this case step down of treatment for psoriasis is possible.     

Hyaluronan in wound healing: Rediscovering a major player

Wound healing involves a series of carefully modulated steps, from initial injury and blood clot to the final reconstituted tissue or scar. A dynamic reciprocity exists throughout between the wound, blood elements, extracellular matrix, and cells that participate in healing. Multiple cytokines and signal transduction pathways regulate these reactions. A major component throughout most of the process is hyaluronan, a straight‐chain carbohydrate extracellular matrix polymer. Hyaluronan occurs in multiple forms, chain length being the only distinguishing characteristic between them. Levels of hyaluronan in its high–molecular‐weight form are prominent in the earliest stages of wound repair. Progressively more fragmented forms occur in a manner not previously appreciated. We outline here steps in the wound healing cascade in which hyaluronan participates, as well as providing a review of its metabolism. Although described by necessity in a series of quantum steps, the healing process is constituted by a smooth continuum of overlapping reactions. The prevalence of hyaluronan in the wound (initially termed “hexosamine‐containing mucopolysaccharide”), particularly in its early stages, was pointed out over half a century ago by the Harvard surgeon J. Engelbert Dunphy. It appears we are now returning to where we started.     

Phagocytized corpora amylacea as a histological hallmark of astrocytic injury in neuromyelitis optica

Neuromyelitis optica (NMO) is an inflammatory demyelinating and necrotizing disorder of the CNS that mainly affects the optic nerve and spinal cord. The etiology is still uncertain; however, the discovery of serum anti‐aquaporin‐4 (AQP4) autoantibody is becoming the center of attention, and a new hypothesis is emerging that NMO is essentially astrocytopathy provoked by this autoantibody. In this study, we focused on corpora amylacea (CA), glycoproteinaceous inclusions in astrocytic processes. We examined 57 lesions in nine cases of NMO spectrum disorder, and demonstrated that CA were phagocytized by macrophages in 42 lesions (74%) of eight cases, while phagocytized figures were not seen in unaffected areas. Phagocytized CA were frequently encountered in early‐phase lesions still retaining myelin structures, while fewer or none were found in chronic destructive lesions. Moreover, phagocytized CA were significantly smaller in diameter than intact ones, and CA were decreased or absent in most lesions assessed. These findings suggest the following pathophysiological process: the astrocytes are affected at an early phase in NMO, CA are expelled from the astrocytes and phagocytized by macrophages finally leading to clearance. A phagocytized figure and subsequent loss of CA can be a histological hallmark of astrocytic injury of NMO.     

Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages

Together with regulatory T cells (Tregs), tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte‐derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD‐L1 and chemokines by CD163⁺ CD206⁺ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD‐L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD‐L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T‐cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.